FDA ECT Summary Report Blind Spots

At the end of today’s hearings, an FDA advisory panel will issue recommendations about whether manufacturers of electroconvulsive devices must put their devices to rigorous safety tests or whether they should be reclassified from Class III (high risk) to Class II (moderate risk)>

Below are critical comments by Professor John Read (University of Auckland, New Zealand) about FDA’s Summary of Electroconvulsive devices.

Of note, although 103 deaths were reported to the FDA in individual submissions, the FDA report devotes merely half a page to this issue.

Does that not demonstrate a disregard for the value of the lives of those who are subjected to ECT–most often against their will ?

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January 28, 2011: Media Release:

FDA REPORT on ELECTROSHOCK UNDER-ESTIMATES MORTALITY AND MEMORY LOSS Professor John Read (University of Auckland, New Zealand) has submitted to the FDA ‘Commentary’ of the FDA’s 150 page ‘Executive Summary’ report – released on the eve of its hearings about Electroshock Therapy (Jan 27-28).

The five page Commentary (available on request: j.read@auckland.ac.nz) states, in relation to effectivness,‘The FDA staff seem to have conducted a comprehensive review of the available research. They reach broadly similar conclusions to that of our own recent review’, namely: ‘Little evidence exists supporting the long-term effectiveness of ECT’ (FDA Report))

Suicide Prevention

The belief that ECT somehow prevents suicide has long been a central plank of claims that it is effective made by ECT proponents. The Commentary notes that the FDA reports no studies at all in support of this claim. There are none. There were, however, 43 individual submissions to the FDA citing suicidality as an adverse effect (p 68).

Deaths

The FDA report devotes only half a page to this issue.

A claim first made by the American Psychiatric Association (2001) is repeated verbatim by the FDA: ‘mortality rate of 1:10,000 patient, or 1:80,000 treatments’.

Our literature review (Read & Bentall, 2010) found numerous studies with mortality rates far in excess of that claimed by the APA and reproduced, rather uncritically, by the FDA.

103 deaths were reported to the FDA in individual submissions “The FDA report appears to have significantly underestimated the mortality rate of ECT.”

Memory Loss

The FDA report fails to include the best designed study to date assessing autobiographical memory. Despite repeated claims, for 50 years, that ECT is safe, the first large-scale prospective study of cognitive outcomes following ECT did not occur until 2007. Prominent ECT advocate Harold Sackeim, found that autobiographical memory was significantly worse than pre-ECT levels six months later. At both times the degree of impairment was significantly related to the number of shocks.

[The Sackeim study was formally submitted to the FDA, by JR, on Dec. 30, 2010, with the Read & Bentall literature review – which is also uncited]

A New Zealand Government report, commissioned by the Ministry of Health concluded that “ECT may permanently affect memory” (Ministry of Health, 2004) and bemoans the “slowness in acceptance by some professional groups that such outcomes are real and significant in people’s lives”.

Even the 2001 APA Report has acknowledged that “In some patients the recovery from retrograde amnesia will be incomplete, and evidence has shown that ECT can result in persistent or permanent memory loss”.

The Commentary concludes: “The FDA report has grossly underestimated the duration of the memory deficits caused by ECT”.

‘Subjective’ Memory Loss

“The FDA report also repeats the claim that much of the memory loss is related to the depression rather than to the ECT, using the term ‘subjective memory loss’ employed by by ECT proponents to promote this hypothesis. Our review points out that this oft-made claim has been repeatedly demonstrated to be unsubstatantiated.”

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COMMENTARY ON FDA REPORT PREPARED FOR MEETING OF THE NEUROLOGICAL DEVICES PANEL ON ELECTROSHOCK THERAPY AND DEVICES – JANUARY 27-28, 2011

Submitted to FDA January 26,2010

Professor John Read, University of Auckland, New Zealand. January 26, 2011.

Note: This commentary focuses primarily on the research using sham/simulated ECT vs real ECT methodology – which is unanimously agreed to be the best available design to control for the powerful placebo effects associated with ECT. See Read and Bentall (2010).

EFFECTIVENESS FDA staff seem to have conducted a comprehensive review of the available research. They reach broadly similar conclusions to that of our own recent review, namely:

‘For depression, after one month, the limited available evidence does not support the conclusion that that ECT is more effective than sham’.

Our own literature review concurred, i.e. ECT has no beneficial effects beyond the actual treatment period. We found, however, that even those short term advantages over sham ECT were ‘only for some patients, on some measures, sometimes perceived only by psychiatrists and not by other raters’.

Schizophrenia (for whichECT was invented, – currently the second most common diagnosis of ECT recipients)

‘ECT for Schizophrenia: In ECT vs. sham comparisons, the effectiveness of ECT and sham were not found to be significantly different.’ (p 42)

Prevention of Suicide

The belief that ECT is life-saving, primarily through its supposed ability to prevent suicide, has long been a central plank of claims that it is effective made by ECT proponents. (For recent examples see statements by Drs Kellner and Fochtman in NYTimes article Jan 23, 2011.)

The FDA reports no studies at all on this issue.

It claims nevertheless, in a Table (p 72), that there is ‘No indication of increased risk in the literature, and some suggestion that risk may decrease’.

The use of the term ‘may’ is far more tentative than the categorical assertions of ECT proponents.

Our review found no properly designed studies supporting this claim, and two studies suggesting an increased risk.

It appears that this claim is particularly immune to the fact that there is no research evidence to support it. The FDA should not repeat this unsubstantiated claim.

There were 43 individual submissions to the FDA citing suicidality as an adverse effect (p 68).

ADVERSE EFFECTS

In this area the conclusions of the FDA report differ from our own conclusions somewhat.

Deaths

The FDA report devotes only half a page to this issue. (p 35-36).

A claim first made by the American Psychiatric Association (2001) is repeated verbatim by the FDA: ‘mortality rate of 1:10,000 patient, or 1:80,000 treatments’. (pp 35, 131)

Our literature review found numerous studies with mortality rates far in excess of that claimed by the APA and reproduced, rather uncritically, by the FDA. The FDA report itself cites one of these; with a death rate of 79:10,000 (18 out of 2,279 patients), i.e. 79 times greater than the APA claim:

‘Nuttall and colleagues (2004) conducted a large retrospective review of ECT. They examined 2,279 patients who underwent 17,394 ECT treatments. Twenty-one patients (0.92%) experienced a complication during their series of ECT (median number of treatments = 7). Cardiac arrhythmias represented the majority of complications. Although there were no occurrences of permanent injury or death immediately after ECT, there were 18 deaths within 30 days of the last treatment.’ (p 36)

However the FDA report goes on to state, despite one of the deaths being a cardiac arrest within two days of ECT, that ‘… none were thought to be related to ECT’. The obvious, but unasked, question here is ‘thought’ by whom?

Elsewhere the FDA report correctly points out that: ‘Cardiovascular complications are one of the most frequent causes of significant morbidity and mortality associated with ECT (p 19).

The FDA also repeats the APA claim that the mortality rate ‘is estimated to be approximately the same as the rate associated with minor surgery’ (p 35). Even if this were true of an individual administration of ECT (which is unlikely given the cardiovascular and other complications specific to ECT) the claim ignores the rather obvious fact that a course of ECT averages about eight adminstrations of the procedure, and that the actual risk is, therefore, several times higher than an individual procedure for each ECT recipient.

103 deaths were reported to the FDA in individual submissions (p 68)

Two of the 151 incidents reported to date by the Manufacturer and User Facility Device Experience (MAUDE) database were deaths

The FDA report appears to have significantly underestimated the mortality rate of ECT.

Memory Loss

Our review and the FDA concur on the fact that the most common adverse effects are in the domain of memory loss.

‘There is clear evidence that memory and cognitive impairment (i.e., orientation, retrograde memory, anterograde memory and global cognitive function) occur both immediately after administration of ECT and following a course of therapy

The two reports differ, however, on the crucial issue of how long the memory dysfunction lasts. The FDA search of the literature seems to be less comprehensive on adverse effects (eg deaths see above) than for effectiveness.

For example, the FDA report fails to include the best designed study to date assessing autobiographical memory. Despite repeated claims, for 50 years, that ECT is safe, the first large-scale prospective study of cognitive outcomes following ECT did not occur until 2007. Prominent ECT advocate Harold Sackeim, found that autobiographical memory was significantly (p < .0001) worse than pre-ECT levels both shortly after ECT (on average 4.4 days) and six months later. At both times the degree of impairment was significantly related to the number of shocks. Women and older people (both of whom are given ECT more frequently) were particularly impaired. Even using a conservative definition of two standard deviations worse than pre-ECT scores, 38 (12.4%) met the criterion for ‘marked and persistent retrograde amnesia’ (Sackeim et al., 2007).

[The Sackeim study was formally submitted to the FDA, by JR, on Dec. 30, 2010, with the Read & Bentall literature review – which is also uncited]

Similarly, although the FDA report cites a literature review that ‘Estimated memory loss ranges from 29% – 79% (Rose et al., 2003)’ (p 22), the report fails to add that the same review found a range for “persistent or permanent memory loss” of 29% to 55%, with a weighted average of 38%.

A New Zealand Government report,commissioned by the Ministry of Health concluded that

“ECT may permanently affect memory” (Ministry of Health, 2004) and bemoans the “slowness in acceptance by some professional groups that such outcomes are real and significant in people’s lives”.

Even the 2001 APA Report has acknowledged that “In some patients the recovery from retrograde amnesia will be incomplete, and evidence has shown that ECT can result in persistent or permanent memory loss”.

the FDA report has grossly underestimated the duration of the memory deficits caused by ECT.

‘Subjective’ Memory Loss

The FDA report also repeats the claim that much of the memory loss is related to the depression rather than to the ECT, using the term ‘subjective memory loss’ employed by by ECT proponents to promote this hypothesis. Our review points out that this oft-made claim has been repeatedly demonstrated to be unsubstatantiated. For example:

Another study (Neylan et al., 2001), which acknowledged that “the memory loss for events immediately preceding, during and after the treatment course can be permanent”, found “no significant correlation between the change in depression rating and the change in any of the 12 cognitive measures”. A recent review concluded that “There is no evidence of a correlation between impaired memory/cognition after ECT and impaired mood, much less a causal relationship” (Robertson & Pryor, 2006).

The only large scale prospective study found no relationship between severity of depression and 19 of the 22 cognitive measures employed (Sackeim et al., 2007).

Neither of these three studies are cited by the FDA report.

The FDA report fails to acknowledge that even if there was a correlation, the causal relationship might have been in the other direction. It can be depressing to lose one’s memory.

MODALITY AND VOLTAGE: A DILEMMA FOR THE FDA

Much of the FDA report is, appropriately, taken up with comparing the effects of bi-lateral (ECT administered across the brain from two electrodes) vs the effects of unilateral ECT, and the effects of a range of voltages.

The findings, consistent with many previous reports, are that bilateral and higher voltages are more effective but that they also carry greater risk of adverse effects, particularly memory and other cognitive dysfunction.

For example:

‘Bilateral electrode placement is associated with a greater risk of cognitive impairment than unilateral electrode placement, and when unilateral electrodeplacement is utilized, high energy ECT dose is associated with a greater risk ofcognitive impairment than low energy dose ECT’ (p 23).

This creates a dilemma for those charged with making regulatory decisions. ECT is at best minimally effective and had serious adverse effects. The logical consequence of the findings about bi-lateral treatment (which remains very common) would be to prohibit any devices capable of administering this particularly damaging form of ECT. However, the minimal effectiveness of ECT can only be improved at the cost of further increasing the probability of memory loss, i.e by using bi-lateral treatment.

This was not a dilemma for the early pioneers of ECT. As our review points out:

In the 1940s it was accepted that ECT worked precisely because it does cause brain damage and memory deficits. In 1941, Walter Freeman, who imported ECT from Europe to the U.S., wrote:

“The greater the damage, the more likely the remission of psychotic symptoms. … Maybe it will be shown that a mentally ill patient can think more clearly and more constructively with less brain in actual operation” (Freeman, 1941). The paper was entitled “Brain damaging therapeutics”. Myerson (1942) explained: “There have to be organic changes or organic disturbances in the physiology of the brain for the cure to take place. I think the disturbance in memory is probably an integral part of the recovery process”.

searched in an attempt to identify all studies comparing ECT with simulated-ECT [SECT]. Results – These placebo controlled studies show minimal support for effectiveness with either depression or ‘schizophrenia’ during the course of treatment (only for some patients, on some measures, sometimes perceived only by psychiatrists and not by other raters), and no evidence, for either diagnostic group, of any benefits beyond the treatment period. There are no placebo-controlled studies evaluating the hypothesis that ECT prevents suicide, and no robust evidence from other kinds of studies to support the hypothesis.

Conclusions – Given the strong evidence (summarised here) of persistent and, for some, permanent brain dysfunction, primarily evidenced in the form of retrograde and anterograde amnesia. and the evidence of a slight but significant increased risk of death, the cost-benefit analysis for ECT is so poor that its use cannot be scientifically justified.

Declaration of Interest: Neither author has any financial conflicts

Ministry of Health (2004). Use of ECT in New Zealand: A Review of Efficacy, Safety and Regulatory Controls. Ministry of Health: Wellington, New Zealand.